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eaction. 125 Therefore, more polar solvents were examined, and the reaction was found to
proceed in DMSO, at 80°C, giving 43% yield of the desired tricyclic lactone 185 as a single
diastereomer. The relative stereochemistry, resulting from endo cycloaddition, was assigned
based on the X-ray crystal structure of a later intermediate 186b (Table 3.4, vide infra). The
cycloaddition could be marginally accelerated by using a mixed solvent system consisting of
DMSO / H2O (2 : 1). Highest yield (50%) of the tricyclic lactone 185 was obtained when the
reaction was performed at lower concentrations (0.01M), suggesting that side reactions may be
responsible for the low yield.
With 185 in hand, we examined its participation in subsequent intermolecular Diels-
Alder reactions (Table 3.4). Reaction with 4-phenyl-[1,2,4]-triazole-3,5-dione was complete in 5
min to afford 186a as a single diastereomer (entry 1). N-Phenylmaleimide reacted at rt within 6 h
to give 186b in 95% yield and diastereoselectivity greater than 10 : 1 (entry 2). The relative
stereochemistry of 186b was established by X-ray crystallography indicating endo approach of
the dienophile from the convex face of the fused tricycle (Appendix C). Maleic anhydride
reacted similarly to give 186c (entry 3). The relatively high reactivity of the diene towards these
activated dienophiles, suggests that less active dienophiles may also undergo the reaction (e.g.
acrolein, methyl vinyl ether, cyclopentenone, etc.); however further studies in that direction were
not pursued.
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